Banu Sarer Yurekli

The efficacy of the semi-blind approach of transversus abdominis plane block on postoperative analgesia in patients undergoing inguinal hernia repair: a prospective randomized double-blind study

Purpose In this prospective, randomized, double-blind study, our aim was to compare the analgesic efficacy of the semi-blind approach of transversus abdominis plane (TAP) block with a placebo block in patients undergoing unilateral inguinal hernia repair. Methods After receiving hospital ethical committee approval and informed patient consents, American Society of Anesthesiologists (ASA) I–III patients aged 18–80 were enrolled in the study. Standard anesthesia monitoring was applied to all patients. After premedication, spinal anesthesia was administered to all patients with 3.5 mL heavy bupivacaine at the L3-L4 subarachnoid space. Patients were randomly allocated into 2 groups. Group I (n = 32) received a placebo block with 20 mL saline, Group II (n = 32) received semi-blind TAP block with 0.25% bupivacaine in 20 mL with a blunt regional anesthesia needle into the neurofascial plane via the lumbar triangle of Petit near the midaxillary line before fascial closure. At the end of the operation, intravenous (IV) dexketoprofen was given to all patients. The verbal analog scale (VAS) was recorded at 2, 4, 6, 12, and 24 hours postoperatively. Paracetamol IV was given to patients if their VAS score > 3. A rescue analgesic of 0.05 mg/kg morphine IV was applied if VA S > 3. Total analgesic consumption and morphine requirement in 24 hours were recorded. Results TAP block reduced VAS scores at all postoperative time points (P < 0.001). Postoperative analgesic and morphine requirement in 24 hours was significantly lower in group II (P < 0.01). Conclusion Semi-blind TAP block provided effective analgesia, reducing total 24-hour postoperative analgesic consumption and morphine requirement in patients undergoing elective unilateral inguinal hernia repair.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy

OBJECTIVE Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Characteristics and Treatment Results of 5 Patients with Fibrous Dysplasia and Review of the Literature.

Aim. Fibrous dysplasia is a rare bone disease caused by missense mutation leading to abnormal fibroblast and osteoblast proliferation and increased bone resorption. FD can present in monostotic or polyostotic forms. About 3% of FD could be in association with McCune-Albright syndrome (MAS). Because FD is a rare disease, there is limited data in the literature about characteristics of disease and response to treatment. Methods. We present our five cases of FD with general properties and their responses to medical treatment. Results. Two of our patients had polyostotic and three had monostotic FD. One of the polyostotic patients had MAS. One of our patients had surgery for femur fractures, facial asymmetry, and findings of compression. Four patients were given pamidronate; one was given zoledronic acid as bisphosphonate treatment. Bone pain was relieved in all patients with medical treatment. Conclusion. There was a decrease in bone turnover markers to some degree with medical treatment but no radiological improvement was observed.

The effect of laparoscopic sleeve gastrectomy on morbid obesity and obesity-related comorbidities: A cohort study

OBJECTIVE Bariatric surgery with multidisciplinary management is a more effective method to treat morbid obesity and obesity-related comorbidities compared with nonsurgical treatments. Laparoscopic sleeve gastrectomy (LSG) was initially performed as the first stage of biliopancreatic diversion with duodenal switch in the super-obese population. In the past few years, however, LSG has been performed as a definitive procedure because of its promising early and midterm results. The aim of this study is to evaluate the efficacy of our initial LSG series of 73 patients on excess weight loss (EWL) and resolution of obesity-related comorbidities in short-term follow-up. MATERIAL AND METHODS From March 2013 to May 2014, 78 morbid obese patients with an average body mass index (BMI) of 46.3 kg/m(2) underwent LSG. There is a 9-month follow-up period on average. Five patients were excluded from the study, because they could not be contacted. Comorbidities, preintervention BMI, glucose, HbA1c, and lipid profiles were recorded at 1, 6, and 12 months postintervention. RESULTS After the surgery, the percent EWL was 58%. The mean serum glucose level, HbA1c level, LDL-cholesterol level, triglyceride level, insulin, and insulin resistance decreased significantly and the mean HDL-cholesterol level increased. CONCLUSION For the resolution of comorbidities, LSG may be used as an effective bariatric and metabolic surgery.

Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat.

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

Assessment of protective effects of pheniramine maleate on reperfusion injury in lung after distant organ ischemia: a rat model.

Objective: The aim of this study is to investigate the protective effects of methylprednisolone (MP) and pheniramine maleate (PM) on reperfusion injury of lungs developing after ischemia of the left lower extremity of rats. Materials and methods: A total of 28 randomly selected male rats were divided into 4 groups, each consisting of 7 rats. Group 1 was the control group. Group 2 was the sham group (ischemia/reperfusion [I/R]). Rats in group 3 were subjected to I/R and given PM (Ph group) and rats in group 4 were subjected to I/R and given MP (Pn group). Results: Malondialdehyde levels were significantly lower in Ph group than in I/R group (P < .05). Superoxide dismutase and glutathione peroxidase enzyme activities were found to be significantly higher in Ph group than in the I/R group (P < .05). Histological examination demonstrated that PM had protective effects against I/R injury. Conclusions: The PM has a protective effect against I/R injury in rat lung.

Is it the time for metformin to take place in adjuvant treatment of Her-2 positive breast cancer? Teaching new tricks to old dogs.

Breast cancer is the most common malignancy diagnosed among women. According to the new molecular subclassification, basal like and Her-2 positive breast cancers have the worst outcome and these are the ones in which chemotherapy is a must as a part of adjuvant treatment. New treatment options that could be used as an adjuvant maintenance treatment are still being investigated. Insulin hormone is one of the reasons of breast cancer recurrence and death in breast cancer survivors. Targeting insulin as a therapeutic modality in breast cancer could be an option in the adjuvant treatment of breast cancer. It seems that insulin may signal to activate a cascade of proliferative and anti-apoptotic events in the cancer cell. Metformin, an oral anti-diabetic known for 50 years, may also have direct effects on cancer cells. Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells. Thus, we believe that the time has arrived both to target insulin reduction and to alter Her-2 oncogene based molecular pathogenetic steps in breast cancer by using metformin as an adjuvant therapy in breast cancer patients.

First metreleptin treatment for generalized lipodystrophy in Turkey.

To the Editor: We report the first patient with generalized lipodystrophy (GL) treated with metreleptin in Turkey. GL is a rare disorder characterized by near total lack of adipose tissue that is associated with ectopic lipid accumulation and hypoleptinaemia. Patients with GL develop metabolic abnormalities associated with insulin resistance in the early years of life. Metreleptin is a recombinant analogue of human leptin which has recently been authorized for the treatment of metabolic complications of leptin deficiency in patients with GL. In a recent paper published in Diabetes Obesity and Metabolism, Vatier et al. reported that metreleptin improves β-cell function in patients with diabetes and lipodystrophy. The authors showed that metreleptin treatment resulted in increased insulin sensitivity during euglycaemic–hyperinsulinaemic clamp, and also increased the disposition index (Acute Insulin Response (AIR) × M-value), which adjusts the acute β-cell function to insulin sensitivity after 1 year of metreleptin. A 22-year-old woman with congenital GL, caused by a homozygous c.144C > A (p.C48*) AGPAT2 mutation, was treated with 5 mg/d of metreleptin for 9 months. She had polycystic ovaries, acanthosis nigricans, hypertension, diabetes, proteinuria, diabetic neuropathy and recurrent acute pancreatitis. She was receiving metformin, pioglitazone, gemfibrozil, fish oil, ramipril, and 210 units/d of insulin. She had also previously received multiple courses of plasmapheresis for hypertriglyceridaemia. Her basal leptin level was 0.1 ng/mL. Metreleptin acted rapidly on glycaemic control which, we believe, was mostly affected by appetite control during the 1st month of treatment (Figure 1A). In the following months, we observed a gradual improvement in her glycaemic control, along with a decrease in the amount of insulin that she used (Figure 1B). The need for insulin disappeared on the 9th month of treatment. On her latest visit, we observed that glycated haemoglobin remained at target levels after insulin discontinuation for 2 months. Insulin resistance, represented by homeostatic model assessment of the insulin resistance index, decreased from 6.53 to 1.06. Insulin secretion measured by the ratio of the area under the insulin curve to the area under the glucose curve (AUCins/ glu) on mixed-meal tolerance test increased. Insulin sensitivity, measured using the Matsuda index, improved after metreleptin treatment, from 3.56 to 12.59. Her insulin secretion-sensitivity index-2 score, the product of insulin secretion represented by AUCins/glu and insulin sensitivity represented by Matsuda index, increased from a baseline level of 0.12 to 2.87 by the 9th month of treatment. Triglyceride levels dropped progressively, starting from the 1st weeks of treatment (Figure 1C). Hepatic steatosis improved significantly (Figure 1D). The regression in abdominal protrusion caused by hepatomegaly was remarkable even on physical examination (Figure 1E). We observed a dramatic decrease in proteinuria which was at extreme levels before treatment (Figure 1F). Excessive sweating secondary to hypermetabolic state, which was associated with leptin deficiency, disappeared by the 5th month of treatment. No treatment-related side effect was observed. We previously reported that the prevalence of congenital GL in Turkey is higher than the worldwide prevalence of this condition as a result of relatively high rates of consanguineous marriages. Our first experience shows that metreleptin treatment leads to a dramatic improvement in metabolic control, ectopic lipid accumulation, proteinuria and appetite control. Metreleptin has an orphan drug designation in the European Union, and it is available in selected European centres through compassionate programmes. Metreleptin was provided by such a local compassionate-use agreement in this particular case. As members of the Turkish Lipodystrophy Study Group, we are looking forward to the opportunity of using metreleptin in all Turkish patients with GL, either through standard reimbursement protocols approved by the national authorities or through a wider national compassionate-use agreement between the authorities and supplier.

A novel CYP11B1 mutation in a Turkish patient with 11β-hydroxylase deficiency: An association with the severe hypokalemia leading to rhabdomyolysis

ABSTRACT Congenital adrenal hyperplasia is an autosomal recessive disorder caused by the loss of one of five steroidogenic enzymes affecting cortisol synthesis. In deficiency of 11 β- hydroxylase, 11-Deoxycortisol cannot be converted to cortisol and deoxycorticosterone cannot be converted to corticosterone. We present our 11β-hydroxylase deficiency case with hypokalemia and with a novel mutation. A 20-year-old male patient who’d been on steroid replacement treatment for adrenal insufficiency for 18 years was admitted with spasm, dyspnea and syncope attacks. On laboratory examination his potassium level was 1.4 meq/L and creatinine kinase and myoglobin levels were increased indicating rhabdomyolysis. Potassium infusion was started. 11 β- hydroxylase deficiency related congenital adrenal hyperplasia was diagnosed as the patient had adrenal insufficiency, hypertension and hypokalemia. Spironolactone treatment was started in addition to potassium infusion. Potassium levels were back to normal in the follow-up. Hypokalemia-related rhabdomyolysis regressed. In CYP11B1 whole genome sequencing analysis, p.A199P and p.R448H compound heterozygous mutation was detected. Thus, these two compound heterozygous mutations may be associated with the severity of the disease.

A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA) mutation in exon 1 (D47N)

BACKGROUND Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat which is associated with insulin resistant diabetes. The Dunnigan variety (FPL2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. CASE REPORT Here, we report on a Turkish family with FPL2 which is caused by a novel heterozygous missense LMNA mutation in exon 1 (D47N, c.139G>A), in the rod domain of lamins A/C. Fat distribution and metabolic features of LMNA D47N mutation were similar to typical codon 482 mutation. Metabolic abnormalities were observed as a form of insulin resistant diabetes, hypertriglyceridemia, low HDL cholesterol and hepatic steatosis. There was no evidence for neuromuscular and cardiac involvement. CONCLUSION Although it is previously known that alterations in the rod domain of type A lamins are involved in cardiac and neuromuscular diseases, our current observation shows that exon 1 LMNA mutations may be associated with partial lipodystrophy without any cardiac and neurological abnormalities, at least at the time of the presentation.